Cancers Evade Immunotherapy by ‘Discarding the Evidence’ of Tumor-Specific Mutations

Excerpt:

“Results of an initial study of tumors from patients with lung cancer or head and neck cancer suggest that the widespread acquired resistance to immunotherapy drugs known as checkpoint inhibitors may be due to the elimination of certain genetic mutations needed to enable the immune system to recognize and attack malignant cells. The study, conducted by researchers on the cells of five of their patients treated at the Johns Hopkins Kimmel Cancer Center, is described online Dec. 28 in Cancer Discovery.”

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Immunotherapy Looks ‘Promising’ in Malignant Mesothelioma

Excerpt:

“Immunotherapy is now offering hope even in one of the most aggressive cancers of all, malignant pleural mesothelioma.

“Malignant mesothelioma is usually diagnosed at a late stage and is essentially incurable. The median overall survival is approximately 12 months with first-line chemotherapy, and median survival with second-line therapy, which has not yet been adequately defined, is typically less than 10 months.

“Early clinical results with the programmed cell death (PD) inhibitors nivolumab (Opdivo, Bristol-Myers Squibb) and pembrolizumab (Keytruda, Merck & Co) show response, yielding survival rates that appear to be improvements on what has been seen historically with chemotherapy.”

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Neoadjuvant Nivolumab Appears Safe and Feasible in Lung Cancer

Excerpt:

“Neoadjuvant immunotherapy with the programmed cell death protein 1 (PD-1) inhibitor nivolumab (Opdivo) is safe and feasible in early-stage non–small cell lung cancer (NSCLC). The results come from the first report of PD-1 blockade prior to surgery in this tumor, according to Patrick Forde, MD, of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, who reported these findings at the 2016 European Society for Medical Oncology (ESMO) Congress.”

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Neoadjuvant Nivolumab Appears Safe and Feasible in Lung Cancer

Excerpt:

“Neoadjuvant immunotherapy with the programmed cell death protein 1 (PD-1) inhibitor nivolumab (Opdivo) is safe and feasible in early-stage non–small cell lung cancer (NSCLC). The results come from the first report of PD-1 blockade prior to surgery in this tumor, according to Patrick Forde, MD, of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, who reported these findings at the 2016 European Society for Medical Oncology (ESMO) Congress.

” ‘Thirty-nine percent of patients with early-stage NSCLC treated with two doses of nivolumab had major pathologic responses associated with immune cell infiltration of tumor,’ Dr. Forde reported. ‘One hypothesis is that having tumor in situ when you give anti–PD-1—having more antigen present—may be better than giving it in the adjuvant setting, where only micrometastases may be present.’ ”

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Nivolumab Combinations Feasible for Newly Diagnosed GBM

Excerpt:

“The PD-1 inhibitor nivolumab (Opdivo) was successfully combined with radiotherapy alone or concurrently with temozolomide for patients with newly-diagnosed glioblastoma multiforme (GBM) in cohorts 1c and 1d from the phase I CheckMate-143 study, according to findings presented at the 2016 Society for Neuro-Oncology Annual Meeting.

” ‘The research question was if treatment with nivolumab to block immune checkpoint pathways could potentiate an antitumor immune response and have synergistic effects with radiotherapy or chemoradiotherapy in patients with newly diagnosed GBM,’ stated first author by Antonio Omuro, MD, of the Memorial Sloan Kettering Cancer Center.”

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Phase 1/2 Data Combining Urelumab with Opdivo (Nivolumab) in Hematologic and Solid Tumors Suggest Increased Antitumor Effect in Patients with Melanoma

Excerpt:

Bristol-Myers Squibb Company BMY -0.86% today announced safety and efficacy data from a Phase 1/2 study of urelumab in combination with Opdivo (nivolumab) in patients with hematologic and solid tumors, including biomarker analyses by level of PD-L1 expression. The combination of urelumab and Opdivo showed encouraging efficacy among 46 evaluable melanoma patients with an objective response rate (ORR) of 50% (23/46 with 18 confirmed and 5 unconfirmed). ORR was a secondary endpoint as measured by Response Evaluation Criteria In Solid Tumors (RECIST). Similar response was seen in both PD-L1 positive and PD-L1 negative melanoma patients, with ORR of 50% (10/20) and 47% (8/17) in those with greater-than or equal to 1% and <1% PD-L1 expression, respectively. Among the other cohorts (n=78), one non-small cell lung cancer (NSCLC) patient and one squamous cell carcinoma of the head and neck (SCCHN) patient had an objective response. In the full patient population (n=138), no significant added toxicity was observed with urelumab in combination with Opdivo over Opdivo monotherapy. These data were presented at an oral presentation (poster number 239) at the Society for Immunotherapy of Cancer (SITC) 31 Annual Meeting on November 12 at 10:40 a.m. EST in National Harbor, Maryland.”

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Nivolumab Combos Explored in First-Line NSCLC Trial

Excerpt:

“Although nivolumab (Opdivo) has demonstrated a clear survival advantage compared with chemotherapy in patients with progressive non–small cell lung cancer (NSCLC) who express PD-L1 in their tumor cells, the same cannot be said for those who are PD-L1–negative.

“As a result, researchers are seeking to elicit antitumor activity in a broader range of patients, notably through a multiarm trial evaluating the PD-1 inhibitor along with combinatorial approaches.

“CheckMate-227 (NCT02477826) is a phase III, open-label, randomized trial for patients with chemotherapy-naïve stage IV or recurrent NSCLC. The trial will enroll patients into separate groups according to PD-L1 expression status (≥1% or <1%).”

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in a First, U.S. Trial to Test Cuban Lung-Cancer Vaccine

Excerpt:

“The Food and Drug Administration has approved the first clinical trial to test a Cuban drug in the United States — a lung-cancer vaccine developed in Havana.

“The decision on the early-stage trial was announced Wednesday by New York Gov. Andrew Cuomo (D) and officials at the Roswell Park Cancer Institute, based in Buffalo. The trial could start as soon as next month and will enroll 60 to 90 patients. It is likely to take three years to complete.

“The trial will test the CIMAvax-EGF vaccine, combined with an immunotherapy drug called Opdivo, which has already been approved in the United States. The goal is to see if the pairing improves effectiveness.”

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War of the Checkpoint Inhibitors: Anti-PD-1 Drugs Move into First-Line Treatment in NSCLC


Last year, the U.S. Food and Drug Administration (FDA) approved two anti-PD-1 checkpoint inhibitors, a type of immunotherapy, for treatment of non-small cell lung cancer (NSCLC) in patients whose cancer has progressed after first-line treatment with chemotherapy. Now, the manufacturers of both drugs, pembrolizumab (made by Merck) and nivolumab (made by Bristol-Myers Squibb; BMS) are intent on expanding the indications for use of their drugs. To this end, they have conducted clinical trials testing each as a first-line treatment (i.e., in previously untreated patients), comparing them to standard chemotherapy. Continue reading…